Giovanni Taffurelli

Laparoscopic Distal Pancreatectomy in Benign or Premalignant Pancreatic Lesions: Is It Really More Cost-Effective than Open Approach?

BackgroundData regarding the quality of life in patients undergoing laparoscopic distal pancreatectomy are lacking and no studies have reported a real cost-effectiveness analysis of this surgical procedure. The aim of this study was to evaluate and compare the quality of life and the cost-effectiveness of a laparoscopic distal pancreatectomy with respect to an open distal pancreatectomy.MethodsForty-one patients who underwent a laparoscopic distal pancreatectomy and 40 patients who underwent an open distal pancreatectomy were retrospectively studied as regards postoperative results, quality of life and cost-effectiveness analysis. The Italian neutral version of the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire C-30, version 3.0, was used to rate the quality of life.ResultsPostoperative results were similar in the two groups; the only difference was that the first oral intake took place significantly earlier in the laparoscopic group than in the open group (P < 0.001). Regarding quality of life, the laparoscopic approach was able to ameliorate physical functioning (P = 0.049), role functioning (P = 0.044) and cognitive functioning (P = 0.030) and reduce the sleep disturbance scale (P = 0.050). The cost-effectiveness analysis showed that the acceptability curve for a laparoscopic distal pancreatectomy had a higher probability of being more cost-effective than an open distal pancreatectomy when a willingness to pay above 5400 Euros/quality-adjusted life years (QALY) was accepted.ConclusionDespite the limitations of the study, laparoscopic distal pancreatectomy can be considered not only safe and feasible but also permits a better quality of life and is acceptable in terms of cost-effectiveness to Italian and European health care services.

Pancreatic resection in patients 80 years or older: a meta-analysis and systematic review.

Objective The aim of this study was to evaluate the safety of pancreatic resections in patients 80 years or older. Methods A systematic search of the literature was carried out that compared perioperative outcomes after pancreatic resection in patients 80 years or older with patients younger than 80 years. The primary end points were postoperative mortality and morbidity. The secondary end points were incidence of postoperative pancreatic fistula, delayed gastric emptying, bile leak, pneumonia, postoperative infection, cardiologic complications, reoperation, and length of hospital stay. Results Nine studies were found to be suitable for the meta-analysis. The postoperative mortality and morbidity were significantly higher in the group 80 years or older (P < 0.00001 and P = 0.003, respectively) except for patients in whom there were no differences in preoperative comorbidities (P = 0.56 and P = 0.36, respectively). Postoperative cardiac complications were significantly more frequent in patients 80 years or older (P < 0.0001), and the length of hospital stay was significantly longer in octogenarian patients (P = 0.008). Conclusions Patients 80 years or older have an increased incidence of postoperative mortality, morbidity, and cardiac complications and a longer length of hospital stay than do younger patients. Thus, pancreatic resection can be recommended only in a selected group of patients 80 years or older.

Assessment of Complications According to the Clavien-Dindo Classification After Distal Pancreatectomy

CONTEXT The absence of a definition and a widely accepted ranking system to classify surgical complications has hampered proper interpretation of the surgical outcome. PATIENTS Sixty-one patients undergoing distal pancreatectomy. MAIN OUTCOME MEASURES The complications were classified according to the Clavien-Dindo classification; each grade was evaluated regarding the length of the postoperative stay and was compared to the most important complications. RESULTS Thirty (49.2%) patients had no complications; out of the thirty-one (50.8%) patients with complications, 9 (14.5%) had grade I, 15 (24.6%) had grade II, 6 (9.8%) had grade III, and 1 (1.6%) had grade IV. There were no postoperative deaths (grade V). A progressive increase in the length of hospitalization from patients with no complications to those having grade IV (P < 0.001) was noted. Postoperative pancreatic fistula and postpancreatectomy hemorrhage rates did not significantly increase from Clavien-Dindo grade I to grade IV (P = 0.118 and P = 0.226, respectively). The severity of a postpancreatectomy hemorrhage, instead, was positively related to the grade of the Clavien-Dindo classification (P = 0.049) while postoperative pancreatic fistula resulted near the significant value (P = 0.058). CONCLUSIONS The Clavien-Dindo classification is a simple way of reporting all complications following distal pancreatectomy. It allows us to distinguish a normal postoperative course from any deviation and the severity of complications and it may be useful for comparing postoperative morbidity between different pancreatic centers.

Asymptomatic Cholecystocolonic Fistula: A Diagnostic and Therapeutic Dilemma

Cholecystocolonic fistulas (CCF) are rare complications of gallstones with a variable clinical presentation. Despite modern diagnostic tools, cholecystocolonic fistulas are often asymptomatic and it is difficult to diagnose them preoperatively. Biliary-enteric fistulae have been found in 0.9% of patients undergoing biliary tract surgery. The most common site of communication of the fistula is the cholecystoduodenal (70%), followed by the cholecystocolic (10–20%), and the least common is the cholecystogastric fistula. Herein, we report a case of female patient with multiple episodes of acute recurrent cholangitis due to common bile duct and gallbladder stones in which preoperative imaging studies were negative for cholecystocolonic fistula that was incidentally discovered and treated during surgery and was appropriately treated. A review of the literature is reported too.

Laparoscopic distal pancreatectomy: many meta-analyses, few certainties.

In recent years, an increasing of the level of evidence occurred with a significant number of meta-analyses. A question remains open: can LDP be considered the “new gold standard” for benign and malignant body–tail pancreatic disease? A systematic literature search was conducted to identify all meta-analyses published up to 2016. The primary endpoint was to evaluate the clinical safety of LDP. The secondary endpoints were to evaluate: the length of hospital stay (LOS), readmission rate, postoperative pancreatic fistula (POPF), overall postoperative morbidity and oncologic safety. Nine studies were found to be suitable for the analysis. Data regarding clinical safety were extractable in all meta-analyses but a “between study” homogeneity was available only in 7. The safety of LDP was sustained by six meta-analyses in benign/low grade of malignancy body–tail pancreatic lesions, by one in ductal adenocarcinoma (PDAC). LDP has a shorter LOS compared to open distal pancreatectomy (ODP), demonstrated by three meta-analyses. Readmission rate in LDP procedures was lower than in ODP; these data are sustained by one meta-analysis. LDP is not inferior to ODP regarding the occurrence of POPF (seven meta-analyses); overall morbidity rate was lower in LDP than ODP for benign or low-grade malignant tumor. The use of the LDP in PDAC is sustained from one study. In conclusion, LDP can be considered a safe alternative to ODP. LDP could have some advantages but the data do not permit to define this procedure as the first choice or as the new gold standard.

Risk Factors for Malignancy of Branch-Duct Intraductal Papillary Mucinous Neoplasms: A Critical Evaluation of the Fukuoka Guidelines With a Systematic Review and Meta-analysis.

Objectives This study aimed to evaluate the accuracy of the risk factors proposed by Fukuoka guidelines in detecting malignancy of branch-duct intraductal papillary mucinous neoplasms. Method Diagnostic meta-analysis of cohort studies. A systematic literature search was conducted using MEDLINE, the Cochrane Library, Scopus, and the ISI-Web of Science databases to identify all studies published up to 2014. Results Twenty-five studies (2025 patients) were suitable for the meta-analysis. The “high risk stigmata” showed the highest pooled diagnostic odds ratio (jaundice, 6.3; positive citology, 5.5; mural nodules, 4.8) together with 2 “worrisome features” (thickened/enhancing walls, 4.2; duct dilatation, 4.0) and 1 “other parameters” (carbohydrate antigen 19-9 serum levels, 4.6). Conclusions An “ideal risk factor” capable of recognizing all malignant branch-duct intraductal papillary mucinous neoplasms was not identified and some “dismal areas” remain. However, “high risk stigmata” were strongly related to malignancy, mainly enhancing mural nodules. Among the “worrisome features,” duct dilatation and thickened/enhancing walls were underestimated, and their diagnostic performance was similar to those of “high risk stigmata.” The carbohydrate antigen 19-9 serum level should be added to the Fukuoka algorithm because this value could help in carrying out correct management.

Characterization of pancreatic ductal adenocarcinoma using whole transcriptome sequencing and copy number analysis by single-nucleotide polymorphism array

The aim of the current study was to implement whole transcriptome massively parallel sequencing (RNASeq) and copy number analysis to investigate the molecular biology of pancreatic ductal adenocarcinoma (PDAC). Samples from 16 patients with PDAC were collected by ultrasound‑guided biopsy or from surgical specimens for DNA and RNA extraction. All samples were analyzed by RNASeq performed at 75x2 base pairs on a HiScanSQ Illumina platform. Single‑nucleotide variants (SNVs) were detected with SNVMix and filtered on dbSNP, 1000 Genomes and Cosmic. Non‑synonymous SNVs were analyzed with SNPs&GO and PROVEAN. A total of 13 samples were analyzed by high resolution copy number analysis on an Affymetrix SNP array 6.0. RNAseq resulted in an average of 264 coding non‑synonymous novel SNVs (ranging from 146‑374) and 16 novel insertions or deletions (In/Dels) (ranging from 6‑24) for each sample, of which a mean of 11.2% were disease‑associated and somatic events, while 34.7% were frameshift somatic In/Dels. From this analysis, alterations in the known oncogenes associated with PDAC were observed, including Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations (93.7%) and inactivation of cyclin‑dependent kinase inhibitor 2A (CDKN2A) (50%), mothers against decapentaplegic homolog 4 (SMAD4) (50%), and tumor protein 53 (TP53) (56%). One case that was negative for KRAS exhibited a G13D neuroblastoma RAS viral oncogene homolog mutation. In addition, gene fusions were detected in 10 samples for a total of 23 different intra‑ or inter‑chromosomal rearrangements, however, a recurrent fusion transcript remains to be identified. SNP arrays identified macroscopic and cryptic cytogenetic alterations in 85% of patients. Gains were observed in the chromosome arms 6p, 12p, 18q and 19q which contain KRAS, GATA binding protein 6, protein kinase B and cyclin D3. Deletions were identified on chromosome arms 1p, 9p, 6p, 18q, 10q, 15q, 17p, 21q and 19q which involve TP53, CDKN2A/B, SMAD4, runt‑related transcription factor 2, AT‑rich interactive domain‑containing protein 1A, phosphatase and tensin homolog and serine/threonine kinase 11. In conclusion, genetic alterations in PDCA were observed to involve numerous pathways including cell migration, transforming growth factor‑β signaling, apoptosis, cell proliferation and DNA damage repair. However, signaling alterations were not observed in all tumors and key mutations appeared to differ between PDAC cases.

Portal/Superior Mesenteric Vein Reconstruction during Pancreatic Resection Using a Cryopreserved Arterial Homograft.

Background: Portal-superior mesenteric vein (PV/SMV) resection during pancreatic resection has been widely applied in clinical practice. Methods: From a prospective data base of pancreatic resections, patients undergoing PV/SMV resection and reconstruction with a cryopreserved arterial homograft were extracted with the aim of evaluating the safety, feasibility and reproducibility of the procedure. Data regarding patient demographics, preoperative staging, surgery, histopathology and postoperative outcomes were analyzed. Results: Five patients were extracted in the last year. Indications for this technique were type IV-V degree of vein involvement and a 3.5 cm median length of vein infiltration. Median operative and clamping times were satisfactory (385 and 27 min, respectively), postoperative outcomes were good and there was no graft infection, thrombosis or stenosis occurred postoperatively and during the follow-up period. Conclusion: The use of a cryopreserved arterial homograft for PV/SMV reconstruction after pancreatic resection seems to be a feasible, safe and easily reproducible surgical technique in high-volume specialized centers and can be added to the pool of surgical solutions in selected patients.

Minimally Invasive Pancreaticoduodenectomy: What is the Best "Choice"? A Systematic Review and Network Meta-analysis of Non-randomized Comparative Studies.

BackgroundMany mini-invasive pancreaticoduodenectomy (MIPD) techniques have been reported, but their advantages with respect to an open technique (OPD) and with respect to each other are unclear.MethodA systematic literature search of studies comparing different types of MIPD was carried out: laparoscopic-assisted (LAPD), totally robotic (TRPD), totally laparoscopic (TLPD) or totally laparoscopic—robotic assisted (TLPD-RA) to OPD. The primary endpoint was postoperative mortality. The secondary endpoints were intraoperative, postoperative and oncological outcomes. A network meta-analysis was designed to generate direct, indirect and mixed estimate effects, between different approaches, for each variable. The effects were reported as pairwise comparisons and hierarchical ranking as to each approach could be the best or the worst for each outcome, expressed by the surface under the cumulative ranking curve.ResultsTwenty studies were identified, involving 2759 patients: 1813 OPDs, 81 LAPDs, 505 TRPDs, 224 TLPDs and 136 TLPD-RAs. No differences regarding postoperative mortality were found in pairwise comparison. The LAPD technique had a high probability of being the worst approach, while TRPD had a high probability of being one of the best. Regarding the secondary endpoints, OPD was the best regarding operative time and postoperative bleeding, but the worst regarding blood loss and wound infection. The TRPD or TLPD-RA techniques seemed to be the best for delayed gastric emptying, length of hospital stay, harvested lymph nodes and postoperative morbidity. The TLPD technique was often the worst approach, especially for overall and major complications, postoperative bleeding and biliary leak.ConclusionThe safest MIPDs are those involving a robotic system which seems to have a promising role in ameliorating the outcomes of OPD, especially when compared to a laparoscopic approach.

Estimation of the Survival Benefit Obtainable From Screening for the Early Detection of Pancreatic Cancer.

ObjectiveThe chance to improve survival from pancreatic adenocarcinoma relies on early diagnosis through screening, but any screening program is subject to lead-time bias and no data are available in this regard. Aim of the present study was to evaluate the benefit obtainable from a screening program for early detection of pancreatic adenocarcinoma, considering screen-related biases. MethodsMonte Carlo simulation was performed using data from 1000 pancreatic cancer patients admitted in a tertiary referral hospital and from pertinent literature. Lead-time bias was assessed and subtracted from expected survival. ResultsMean expected life expectancy was 13.0 months. Assuming a 20%, 30%, or 50% stage III/IV reduction with screening, pancreatic resections would increase from 217 to 290 in front of a 20% stage III/IV reduction to 324 in front of a 30% reduction and to 385 in front of a 50% reduction. After lead-time adjustment, life expectancies were 14.0, 14.6, and 15.9 months, respectively. The number-needed-to-screen calculation suggests that screening can be harmful in a proportion of patients inversely dependent on the length of follow-up and a significant improvement of survival after diagnosis. ConclusionsPancreatic adenocarcinoma screening program would probably be successful in the presence of a considerable improvement of postdiagnostic survival; otherwise, it only increases surgical procedure amount.